The mechanisms responsible for the alteration of chemical carcinogenesis by the dietary lipotropes, choline, methionine, folic acid and vitamin B-12, have been studied. The metabolism and carcinogenic activity of ethionine in different species is being compared. Correlations between the tissue levels of the physiological methyl donor S-adenosylmethionine, its chief metabolic inhibitor, S-adenosylhomocysteine, and 5- methylcytosine in animals treated with carcinogens, liver tumor promoters and methyl-deficient diets are being determined. Using standard bioassays, the effects of (1) the length of time of dietary methyl deprivation, (2) the interaction between methyl deprivation and hepatocarcinogens, and (3) deficiencies of other essential nutrients on hepatocarcinogenesis are under investigation. The effects of carcinogens and methylase inhibitors on the general and specific gene hypomethylation in target tissues are examined.